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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 73 records · Page 4Linked to original sources

An autosomal genomic scan for loci linked to type 2 diabetes in northern Han Chinese.

We report the results of a genome-wide scan conducted in 219 individuals from 34 large multiplex nuclear pedigrees from the northern Han Chinese population at an average resolution of about 10 cM. Nonparametric two-point and multipoint linkage analyses were performed to detect evidence of linkage with type 2 diabetes in this study. On chromosome 1 four regions showed evidence of linkage with type 2 diabetes in northern Han Chinese. Of these regions a marker D1S193 (73 cM) showed evidence of linkage (two-point nonparametric linkage 2.409), and another region (around 190 cM) was a replication of several other studies performed in different ethnic populations. Evidences of linkage have been confirmed by typing additional markers (average distance 1-5 cM) flanking these two positive regions on chromosome 1. We also found indication of linkage with type 2 diabetes on chromosomes 2, 10, 12, 18, 20, and 22 by two-point linkage analyses.

Adult↗

DNA sequence and comparative analysis of chimpanzee chromosome 22.

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

Animals↗

In vivo MRS measurement of liver lipid levels in mice.

A magnetic resonance spectroscopy (MRS) procedure for in vivo measurement of lipid levels in mouse liver is described and validated. The method uses respiratory-gated, localized spectroscopy to collect proton spectra from voxels within the mouse liver. Bayesian probability theory analysis of these spectra allows the relative intensities of the lipid and water resonances within the liver to be accurately measured. All spectral data were corrected for measured spin-spin relaxation. A total of 48 mice were used in this study, including wild-type mice and two different transgenic mouse strains. Different groups of these mice were fed high-fat or low-fat diets or liquid diets with and without the addition of alcohol. Proton spectra were collected at baseline and, subsequently, every 4 weeks for up to 16 weeks. Immediately after the last MRS measurement, mice were killed and their livers analyzed for triglyceride level by conventional wet-chemistry methods. The excellent correlation between in vivo MRS and ex vivo wet-chemistry determinations of liver lipids validates the MRS method. These results clearly demonstrate that in vivo MRS will be an extremely valuable technique for longitudinal studies aimed at providing important insights into the genetic, environmental, and dietary factors affecting fat deposition and accumulation within the mouse liver.

Animals↗

Preparation of metallodielectric composite particles with multishell structure.

In this article, we demonstrated the synthesis of metallodielectric composite particles comprising a metal shell on a dielectric core and an outer coating of an insulating dielectric layer by depositing silver on silica supporting cores followed by coating of titania. A combination of surface reaction and surface seeding techniques is exploited for the formation of a complete silver shell on silica spheres. The additional outer coating of titania on silver shell particles is then performed by hydrolyzing tetra-n-butyl titanate in ethanol at room temperature. The morphologies of silver shells and titania coating are studied with electron microscopy, and their existences are confirmed with X-ray diffraction and energy-dispersive X-ray measurement.

Journal Article↗

Ventral brainstem enterogenous cyst: an unusual location.

Enterogenous cysts mostly locate in the spinal canal and have only rarely been reported in an intracranial site. We report a case of enterogenous cyst in the ventral to brainstem. The 45-year-old woman presented with paroxysmal headache and diplopia. A CT scan and MRI revealed a cystic clival mass from midbrain to medulla. Subtotal resection was performed using a sub-temporal approach and the patient made a good recovery. Pathological examination revealed that the lesion was a typical enterogenous cyst.

Brain Diseases↗

Detection of the putative cis-region involved in the induction by a Pyricularia oryzae elicitor of the promoter of a gene encoding phenylalanine ammonia-lyase in rice.

A rice PAL (phenylalanine ammonia-lyase) gene sequence ( rPAL-P5), which is highly similar to and likely the same as a previously described rice ZB8PAL gene, including the 5'-upstream and exon I coding regions of PAL, was isolated using PCR amplification. The expression of several PALs, including rPAL-P5, was strongly induced following inoculation with Pyricularia oryzae or treatment with a P. oryzae elicitor. To identify the promoter region induced by the P. oryzae elicitor, we constructed and subsequently transformed rPAL-P5 promoter deletion series into rice calli using particle bombardment. Results from both elicitor-inducible reporter gene and gel mobility shift assays demonstrated that the sequence -349 to -256 of the rPAL-P5 promoter includes a cis-element involved in the induction of P. oryzae.

Base Sequence↗

Intermolecular double-quantum coherence MR microimaging of pig tail with unique image contrast.

Image contrast in intermolecular double-quantum coherence (iDQC) imaging of a pig tail was investigated on a 7.05-T microimaging scanner. In addition to TR (repetition time) and TE (echo time), the time interval tau between radio frequency pulses during iDQC evolution and the areas under the iDQC-encode gradients in the iDQC imaging sequence were also used to manipulate image contrast. When suitable imaging parameters were selected, images with unique contrast, such as those with certain regions of the sample highlighted, were obtained without using contrast agents. The effects of iDQC-encode gradient on image contrast were studied quantitatively, and the unique contrast imposed by the related diffusion weighting was also shown. Experimental results demonstrated that the iDQC images have contrast fundamentally different from the conventional single-quantum coherence images.

Animals↗

Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient.

Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

Animals↗

Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation.

The second messenger cyclic adenosine monophosphate (cAMP) plays an important role in cell proliferation, differentiation and apoptosis. In the present work, we evaluated the cAMP signaling in acute promyelocytic leukemia (APL) cells in the context of differentiation induced by all-trans retinoic acid (ATRA). There was a marked increase in the intracellular cAMP level within a few minutes after treatment with ATRA in APL cell line NB4 and fresh APL cells, whereas no such phenomenon was observed in NB4-R1 cells that are resistant to ATRA-induced maturation. In addition, the basal level of intracellular cAMP was lower in NB4-R1 than in NB4 cells. Mechanistic study showed that this induction of cAMP was mediated through the activation of adenylate cyclase. Moreover, we found that cAMP-dependent protein kinase (PKA) activity was quickly upregulated in parallel in ATRA-treated NB4 cells, and the phosphorylation of RARalpha by PKA could increase its transactivation effect. Use of H-89, an inhibitor of PKA, could partially suppress the transcriptional expression of ATRA target genes and ATRA-induced differentiation of APL cells. Taken together, we suggested a crosstalk between ATRA-induced cytosolic pathway and nuclear pathway in APL cell differentiation.

Adenylyl Cyclases↗

Experimental and CFD evidence of multiple solutions in a naturally ventilated building.

This paper considers the existence of multiple solutions to natural ventilation of a simple one-zone building, driven by combined thermal and opposing wind forces. The present analysis is an extension of an earlier analytical study of natural ventilation in a fully mixed building, and includes the effect of thermal stratification. Both computational and experimental investigations were carried out in parallel with an analytical investigation. When flow is dominated by thermal buoyancy, it was found experimentally that there is thermal stratification. When the flow is wind-dominated, the room is fully mixed. Results from all three methods have shown that the hysteresis phenomena exist. Under certain conditions, two different stable steady-state solutions are found to exist by all three methods for the same set of parameters. As shown by both the computational fluid dynamics (CFD) and experimental results, one of the solutions can shift to another when there is a sufficient perturbation. These results have probably provided the strongest evidence so far for the conclusion that multiple states exist in natural ventilation of simple buildings. Different initial conditions in the CFD simulations led to different solutions, suggesting that caution must be taken when adopting the commonly used 'zero initialization'.

Air Movements↗

Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans.

Glucosyltransferases (GTFs) and A cell-surface protein (PAc) are two important virulence factors of the cariogenic organism Streptococcus mutans. They may mediate sucrose-independent or sucrose-dependent attachment of Streptococcus mutans to tooth surfaces, respectively. Thus, inhibiting both virulence factors is predicted to provide better protection against caries than inhibiting a single factor. To develop a highly efficient vaccine against caries, we constructed a fusion DNA vaccine, pGLUA-P, by cloning the GLU region of GTF into a DNA vaccine, pCIA-P, which encodes two highly conservative regions of PAc. In this report, we provide evidence that fewer caries lesions were observed in rats following subcutaneous injection of pGLUA-P, compared with pCIA-P, near the submandibular gland. Our findings suggest that a multigenic DNA vaccine may be more caries-preventive than a single-gene DNA vaccine.

Adhesins, Bacterial↗

Gene expression profiling in human insulinoma tissue: genes involved in the insulin secretion pathway and cloning of novel full-length cDNAs.

Insulinoma is a clinically common cause of organic hypoglycemia. The prominent characteristic of insulinoma is endogenous hyperinsulinism. Until now, the molecular biology of human insulinoma has been little understood. In this study, gene expression profiling of human insulinoma was established by expressed sequence tag (EST) sequencing and cDNA array. A total of 2063 clones were obtained, of these, 1589 clones were derived from EST sequencing, 975 clones were derived from cDNA array and 501 clones were shared by the two methods. G protein alpha-stimulating activity polypeptide (Gsalpha) and carboxypeptidase E (CPE) were the most highly expressed genes in human insulinoma, as derived by EST sequencing and cDNA array respectively. The genes involved in the protein/insulin secretion pathway were strongly expressed in human insulinoma tissue. Meanwhile, eight full-length cDNAs of novel genes were cloned and sequenced. The results demonstrated the molecular biology of human insulinoma tissue at the level of transcript abundance and validated the efficacy of EST sequencing combined with cDNA array in the construction of gene expression profiling. In conclusion, the predominance of the genes participating in the secretory pathway suggested that regulation of secretion might be a major mechanism by which insulin release is abnormally increased in patients with insulinomas. It was also concluded that overexpression of the Gsalpha gene played an important role in the pathogenesis of insulinoma.

Cloning, Molecular↗

Prospective randomised phase II study of gemcitabine at standard or fixed dose rate schedule in unresectable hepatocellular carcinoma.

The present randomised phase II study was an effort to evaluate single-agent gemcitabine as a first-line systemic treatment of Asian patients with unresectable hepatocellular carcinoma (HCC). Gemcitabine was given via intravenous infusion at 1250 mg m(-2) on days 1 and 8 of 3-week cycles. Patients were randomised to receive gemcitabine as a 30-min intravenous infusion (standard schedule) or at a fixed dose rate (FDR) of 10 mg m(-2) min(-1). A total of 50 patients were enrolled in the study, of whom 48 received study therapy. One patient on standard schedule had a partial response, for an overall response rate of 2.1% (95% CI: 0.05-11.1%). The median time to progression and survival time were 46 and 97 days, respectively. The overall rates of Grade 3 or 4 haematological and nonhaematological toxicities were 39.6 and 64.6%, respectively, with no significant difference between the two treatment arms. There were no drug-related deaths and severe clinical toxicities were rare. Both schedules of gemcitabine were safe and toxicity was well manageable in this patient population. However, gemcitabine seems no more active than other cytotoxic agents when used alone for systemic treatment of advanced HCC.

Adult↗

Habitual tea consumption and risk of osteoporosis: a prospective study in the women's health initiative observational cohort.

The purpose of this study was to prospectively investigate associations of habitual drinking of regular tea with bone mineral density and fracture risk. Study participants were a multiethnic postmenopausal cohort (n = 91,465) from the nationwide Women's Health Initiative Observational Study. These women were recruited in the United States and aged 50-79 years at the time of enrollment (1994-1998). The average follow-up time was 4.1 years. Habitual consumption of regular tea was assessed with a structured questionnaire at baseline. Clinical fractures during the follow-up were reported in questionnaires, and hip fractures were further confirmed by reviewing medical records. Bone mineral density measurements were conducted among a subgroup of women (n = 4,979) at three Women's Health Initiative bone mineral density centers using dual-energy x-ray absorptiometry. Multivariate analyses suggested a positive trend of increased total body bone mineral density with tea drinking (p < 0.05). However, results from the Cox proportional hazard models did not show any significant association between tea drinking and the risk of fractures at the hip and forearm/wrist. In conclusion, the results from this study indicate that the effect of habitual tea drinking on bone density is small and does not significantly alter the risk of fractures among the US postmenopausal population.

Aged↗

Differentiation-dependent expression of signal transducers and activators of transcription (STATs) might modify responses to growth factors in the cancers of the head and neck.

Overexpression of the epidermal growth factor receptor (EGFR) in the cancers of the head and neck is well demonstrated. In addition, copy numbers of the EGFR mRNA were significantly higher in poorly differentiated tumors than in tumors that had a differentiated phenotype. Studies by others also showed that the constitutively activated signal transducer and activator of transcription-3 (STAT3), but not STAT1, is required for EGFR-mediated cell growth. Our aim was to reveal if STAT expression is differentiation-dependent and thus, might respond to exogenous stimuli in a differentiation-dependent manner. Both reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry revealed that expression of STAT1 was high in well/moderately differentiated tumors in vivo. In contrast, STAT3 was expressed in poorly differentiated tumors. In vitro experiments showed that differentiated primary oral keratinocytes expressed higher levels of STAT1, but lower levels of STAT3 than did their undifferentiated counterparts. Epidermal growth factor treatment of oral keratinocytes with various degrees of differentiation showed the maximal induction of cyclin D1 in undifferentiated cells. Our findings suggest that the level of differentiation might modulate the outcome of EGFR signaling (i.e. cyclin D1 transcription), due to the differentiation-associated intracellular balance of transcriptional regulators (STAT1 versus STAT3).

Biopsy↗

Bioavailability of an organophosphorus pesticide, fenamiphos, sorbed on an organo clay.

Hydrolysis of an insecticide/nematicide, fenamiphos [ethyl-3-methyl-4-(methylthio)phenyl-(1-methylethyl)phosphoramidate], immobilized through sorption by cetyltrimethylammonium-exchanged montmorillonite (CTMA-clay) by a soil bacterium, Brevibacterium sp., was examined. X-ray diffraction analysis, infrared spectra, and a negative electrophoretic mobility strongly indicated that fenamiphos was intercalated within the bacterially inaccessible interlayer spaces of CTMA-clay. The bacterium hydrolyzed, within 24 h, 82% of the fenamiphos sorbed by the CTMA-clay complex. There was a concomitant accumulation of hydrolysis product, fenamiphos phenol, in nearly stoichiometric amounts. During the same period, in abiotic (uninoculated) controls, 4.6% of the sorbed insecticide was released into the aqueous phase as compared to 6.0% of the sorbed fenamiphos in another abiotic control where activated carbon, a sink for desorbed fenamiphos, was present. Thus, within 24 h, the bacterium hydrolyzed 77% more fenamiphos sorbed by organo clay than the amounts desorbed in abiotic controls. Such rapid degradation of an intercalated pesticide by a bacterium has not been reported before. Evidence indicated that extracellular enzymes produced by the bacterium rapidly hydrolyzed the nondesorbable fenamiphos, even when the enzyme itself was sorbed. Fenamiphos strongly sorbed to an organo clay appears to be readily available for exceptionally rapid degradation by the bacterium.

Adsorption↗

Optical properties of inverted opal photonic band gap crystals with stacking disorder.

We present a detailed study of the effect of planar stacking disorder on optical properties of inverted opal photonic crystals. Systems with periodic stacking sequences are first studied that include face centered cubic, hexagonal close-packed, and doubly hexagonal close-packed photonic crystals. For the structures with periodic stacking order, we evaluate the band structure followed by calculation of transmission spectrum along the direction perpendicular to the hexagonal close-packing plane of the structures. Inverted opal photonic crystals with random stacking sequences are then studied by calculating average transmittance of the photonic crystal slabs over various random stacking configurations. The position and width of the lowest stop gap along the direction normal to the hexagonal close-packing plane is found to be invariant, regardless of the stacking sequence in the photonic crystal. We show how the propagation properties at higher frequencies are affected by the stacking configurations (both periodic and disordered stacking sequences), particularly those near the edges of the absolute band gap. The obtained results are directly relevant to transmission/reflection experiments on inverted opal photonic crystals with complete band gap.

Journal Article↗

Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana.

A neurotoxin, named hainantoxin-IV, was purified from the venom of the spider Selenocosmia hainana. The amino acid sequence was determined by Edman degradation, revealing it to be a 35-residue polypeptide amidated at its C terminal and including three disulfide bridges: Cys2-Cys17, Cys9-Cys24, and Cys16-Cys31 assigned by partial reduction and sequence analysis. Hainantoxin-IV shares 80% sequence identity with huwentoxin-IV from the spider S. huwena, a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels, suggesting that hainantoxin-IV adopts an inhibitor cystine knot structural motif like huwentoin-IV. Under whole-cell voltage-clamp conditions, this toxin has no effect on tetrodotoxin-resistant voltage-gated sodium channels in adult rat dorsal root ganglion neurons, while it blocks TTX-S sodium channels in a manner similar to huwentoxin-IV, and the actions of both toxins on sodium currents are very similar to that of tetrodotoxin. Thus, they define a new family of spider toxins affecting sodium channels.

Amino Acid Sequence↗